Integration of viral DNA sequences into host cell chromosomes is probably a primary event of oncogenesis. The viruses SV40 and adenovirus and the RNA containing rous sarcoma virus can all transform certain rodent cell lines and these transformed cells can be tumorigenic when placed back in the animal. In each of these three cases DNA sequences specific for the respective virus are seen in the host DNA. With SV40 and rous sarcoma virus a double stranded ciruclar DNA molecule is the most likely form that integrates into host sequences. Very little is known about the molecular events when integration occurs with these viruses. We propose to study, at the molecular level, one viral integration sytem. These studies will be conducted on the double stranded circular DNA molecule of phage lambda in cell-free extracts derived from lambda-infected cells. Bacteriophage lambda specifies proteins which can mediate the integration of its circular chromosome into host DNA. Both lambda DNA and the host DNA contain specific sites where integration occurs. The same integration system can also mediate the attachment site. It is this reaction we propose to study since conditions are known where site-specific recombination occurs in vitro. In our studies on the molecular mechanism of integration we will begin (1) the identification and purification of the required cofactors and proteins, (2) determination of DNA structures that are intermediates of the integration process, and (3) isolation and possible sequence determination of the attachment site.